Pseudohypoparathyroidism type 1B

Title

Other Names:

PHP1B

Categories:

Congenital and Genetic Diseases; Endocrine Diseases; Kidney and Urinary Diseases

This disease is grouped under:

Pseudohypoparathyroidism

Summary Summary

Pseudohypoparathyroidism type 1B (PHP1B) is a disorder characterized by lack of response (resistance) to parathyroid hormone (PTH) and other hormones such as thyroid-stimulating hormone (TSH). Resistance mainly occurs in the kidneys, causing low blood calcium levels (hypocalcemia), high blood phosphate levels (hyperphosphatemia), and elevated PTH levels (hyperparathyroidism). Some people with PHP1B also have elevated TSH levels due to TSH resistance.^[1]^[2] Each of these abnormalities can cause a variety of symptoms, which can be viewed by clicking on the terms above.

Severity can vary considerably, even among people in the same family. Symptoms usually begin in childhood due to low calcium levels and may include numbness, seizures, tetany, cataracts, and dental problems.^[1] Excessive growth or weight has been described in some newborns or during early infancy and childhood.^[2] Some children have skeletal problems, such as reduced bone mineral density and osteitis fibrosa.^[1]

The inheritance and genetics of PHP1B is complex. PHP1B is usually sporadic (not inherited), but familial cases with autosomal dominant inheritance, from the mother only, have been reported.^[3] When the parent from which a gene is inherited affects the way a gene acts, it is called genomic imprinting. PHP1B may be caused by randomly inheriting both copies of the long arm of chromosome 20 from the father rather than a copy from each parent (paternal 20q disomy), genetic mutations or epigenetic changes involving the GNAS or STX16 gene, or by unidentified genetic or epigenetic factors.^[1]^[2]

Treatment is lifelong, aiming to normalize calcium and PTH levels with active vitamin D metabolites such as alfacalcidol or calcitriol, and calcium supplementation.^[1]

Last updated: 4/24/2018

Symptoms Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 40 |

Medical Terms	Other Names	Learn More: HPO ID
100% of people have these symptoms
Pseudohypoparathyroidism		0000852
80%-99% of people have these symptoms
Elevated circulating parathyroid hormone level		0003165
Hyperphosphatemia	High blood phosphate levels	0002905
Low urinary cyclic AMP response to PTH administration		0003456
30%-79% of people have these symptoms
Cataract	Clouding of the lens of the eye Cloudy lens [ more ]	0000518
Delayed eruption of teeth	Delayed eruption Delayed teeth eruption Delayed tooth eruption Eruption, delayed Late eruption of teeth Late tooth eruption [ more ]	0000684
Depressed nasal bridge	Depressed bridge of nose Flat bridge of nose Flat nasal bridge Flat, nasal bridge Flattened nasal bridge Low nasal bridge Low nasal root [ more ]	0005280
Full cheeks	Apple cheeks Big cheeks Increased size of cheeks Large cheeks [ more ]	0000293
Hypoplasia of dental enamel	Underdeveloped teeth enamel	0006297
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Round face	Circular face Round facial appearance Round facial shape [ more ]	0000311
Short neck	Decreased length of neck	0000470
Short stature	Decreased body height Small stature [ more ]	0004322
5%-29% of people have these symptoms
Abdominal symptom		0011458
Anxiety	Excessive, persistent worry and fear	0000739
Brachydactyly	Short fingers or toes	0001156
Chest pain		0100749
Conjunctivitis	Pink eye	0000509
Cortical subperiosteal resorption of humeral metaphyses		0003909
Depressivity	Depression	0000716
Diaphyseal sclerosis	Increased bone density in shaft of long bone	0003034
Dyskinesia	Disorder of involuntary muscle movements	0100660
Dyspnea	Trouble breathing	0002094
Hypocalcemic tetany		0003472
Hyporeflexia	Decreased reflex response Decreased reflexes [ more ]	0001265
Increased bone density with cystic changes		0005700
Irritability	Irritable	0000737
Laryngeal dystonia		0012049
Muscle spasm		0003394
Myoclonic spasms		0003739
Obesity	Having too much body fat	0001513
Paresthesia	Pins and needles feeling Tingling [ more ]	0003401
Prolonged QT interval		0001657
Short metacarpal	Shortened long bone of hand	0010049
1%-4% of people have these symptoms
Growth hormone deficiency		0000824
Hypocalcemic seizures	Low calcium seizures	0002199
Pituitary resistance to thyroid hormone		0008227
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
Hypocalcemia	Low blood calcium levels	0002901
Sporadic	No previous family history	0003745

Showing of 40 |

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Last updated: 10/1/2020

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Cause Cause

PHP1B is a complex genetic disorder that may be caused by various types of changes in genes or chromosomes. While there are several different PHP1B subtypes, they all appear to somehow be associated with methylation changes involving the region of the GNAS gene.^[4]

Methylation is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. Abnormal methylation can disrupt the normal activity of genes. For example, for genes that are only "active" when inherited from a certain parent, methylation is one way that a gene's parent of origin is "marked" during the formation of egg and sperm cells.^[5] Changes that affect the activation and deactivation of genes without any change in the underlying DNA sequence are called epigenetic changes.^[6]

Epigenetic changes involving PHP1B can be caused by a maternal deletion in the GNAS or STX16 gene, by paternal uniparental isodisomy of chromosome 20q (patUPD20q) or by undefined genetic mutations. The GNAS methylation changes are ultimately responsible for resistance to PTH signals in part of the kidneys, leading to the features of PHP1B.^[4]

Last updated: 9/22/2016

Inheritance Inheritance

PHP1B is most often sporadic (not inherited), occurring in people with no family history of PHP1B. However, sex-influenced autosomal dominant inheritance, from mother to child, has been reported. When a trait is sex-influenced, it means that the trait is expressed differently depending on whether it is inherited from a person's mother or father.^[3] This phenomenon is known as genomic imprinting.

In familial cases of PHP1B, it appears that parathyroid hormone (PTH) resistance in PHP1B develops only after maternal inheritance of the genetic change, whereas paternal inheritance is not associated with PTH resistance or other endocrine abnormalities.^[3]^[1] In several families with PHP1B, it has been reported that the disorder only occurred if the genetic change was inherited from the mother.^[3]

The genetics of PHP1B is extremely complex. The disorder may be caused by various types of genetic or epigenetic changes. Because the signs and symptoms of the sporadic and autosomal dominant forms of PHP1B are similar, identifying the specific genetic cause in each case is important for determining genetic risks to other family members.^[7]

People with personal questions or concerns about the inheritance of PHP1B, or genetic testing, are strongly encouraged to speak with a genetic counselor or other genetics professional. A genetics professional can help by:

thoroughly evaluating the family history
addressing questions and concerns
assessing recurrence risks
facilitating genetic testing if desired
discussing prenatal testing and management options

Last updated: 4/24/2018

Diagnosis Diagnosis

The diagnosis of PHP1B is generally based on clinical features (signs, symptoms, and physical exams) and biochemical findings from a blood test for calcium-phosphate metabolism. This blood test includes measurements of calcium, phosphate, magnesium, and parathyroid hormone (PTH) in order to distinguish PHP from other conditions.^[8] PHP1B can be distinguished from other types of PHP by the absence of Albright's hereditary osteodystrophy.^[8]^[1] Molecular genetic testing can confirm the diagnosis.^[1]

Last updated: 9/22/2016

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include primary hypoparathyroidism (which can be ruled out by the absence of hypercalciuria), secondary hyperparathyroidism, autoimmune polyendocrinopathy (see this term), and vitamin D deficiency. It should also be excluded from other forms of PHP (see this term) based on the absence of Albright hereditary osteodystrophy (AHO; see this term) and normal expression of Gs protein. Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

Differential diagnoses include primary hypoparathyroidism (which can be ruled out by the absence of hypercalciuria), secondary hyperparathyroidism, autoimmune polyendocrinopathy (see this term), and vitamin D deficiency. It should also be excluded from other forms of PHP (see this term) based on the absence of Albright hereditary osteodystrophy (AHO; see this term) and normal expression of Gs protein.

Visit the Orphanet disease page for more information.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

American Thyroid Association
6066 Leesburg Pike, Suite 550
Falls Church, VA 22041
Toll-free: 800–THYROID (849–7643)
Telephone: 703–998–8890
Fax: 703–998–8893
E-mail: admin@thyroid.org
Website: http://www.thyroid.org
Hormone Health Network
Toll-free: 1-800-HORMONE (1-800-467-6663)
E-mail: hormone@endocrine.org
Website: https://www.hormone.org
Hypopara UK
6 The Meads
East Grinstead
West Sussex, RH19 4DF United Kingdom
Telephone: 01342 316315
E-mail: lizglenister@hypopara.org.uk
Website: http://hypopara.org.uk/home.php
HypoPARAthyroidism Association, Inc. (HPTH )
695 Montecito Ct
Lemoore, CA 93245
Telephone: +1-559-817-7170
E-mail: dmurphy@hypopara.org
Website: https://hypopara.org/
The Endocrine Society
8401 Connecticut Avenue, Suite 900
Chevy Chase, MD 20815
Toll-free: 888–363–6274
Telephone: 301–941–0200
Fax: 301–941–0259
E-mail: societyservices@endo-society.org
Website: http://www.endo-society.org

Social Networking Websites

Visit the Pseudohypoparathyroidism Support Group group on Facebook.

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Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Pseudohypoparathyroidism type 1B. Click on the link to view a sample search on this topic.

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References References

Giovanna Mantovani. Pseudohypoparathyroidism type 1B. Orphanet. October, 2014; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=94089.
Haldeman-Englert CR, Hurst ACE, Levine MA. Disorders of GNAS Inactivation. GeneReviews. October 26, 2017; https://www.ncbi.nlm.nih.gov/books/NBK459117/.
Cassandra L. Kniffin. PSEUDOHYPOPARATHYROIDISM, TYPE IB; PHP1B. OMIM. June 2010; http://omim.org/entry/603233.
Poradosu S, Bravenboer B, Takatani R, Jüppner H. Pseudohypoparathyroidism type 1B caused by methylation changes at the GNAS complex locus. BMJ Case Rep. May 11, 2016; 2016:
Beckwith-Wiedeman syndrome. Genetics Home Reference. June, 2015; https://ghr.nlm.nih.gov/condition/beckwith-wiedemann-syndrome#genes.
Epigenetics. NHGRI Talking Glossary. https://www.genome.gov/glossary/index.cfm?id=528.
HM LUK, IFM LO, TMF TONG, KKS LAI, STS LAM. Pseudohypoparathyroidism Type 1b: First Case Report in Chinese and Literature Review. HK J Paediatr. 2015; 20:32-36.
Valentina Donghi, Stefano Mora, Ilaria Zamproni, Giuseppe Chiumello and Giovanna Weber. Pseudohypoparathyroidism, an often delayed diagnosis: a case series. Cases Journal. 2009; http://www.casesjournal.com/content/2/1/6734.